1. Field of the Invention
The present invention relates to a pharmaceutical composition for treating hypercholesterolemia, and more particularly, to a pharmaceutical composition comprising a bile acid sequestrant resin maintained in a membrane to prevent materials having a higher molecular weight than bile acids from binding to the resin and thereby to enhance the efficiency of the resin in binding bile ids
2. Description of the Prior Art
Hypercholesterolemia, which is commonly known as high blood cholesterol level, can lead to many medical complications such as atherosclerosis. Atherosclerosis is one of the most significant forms of cardiovascular disease because of its frequent occurrence and its predilection for serious ailments such as coronary thrombosis. Atherosclerosis is characterized by the thickening of the intima, reduction in diameter, and loss of elasticity of arteries, due to fatty accumulations. Higher blood levels of cholesterol are observed in atherosclerosis patients than in normal persons. Accordingly, it is considered important in the treatment and prevention of atherosclerosis to maintain normal blood cholesterol levels.
The common therapy for treating hypercholesterolemia, when blood cholesterol levels are not excessively high, but higher than average, has been the consumption of a low fat diet, devoid as much as possible of animal fats. This necessitates reduced consumption of nutritious foods such as meat, milk and eggs. Although maintenance of a low fat diet can help control hypercholesterolemia in a large number of instances, for some individuals, additional means are required to lower the blood cholesterol level.
One of the major uses of cholesterol in the body is to serve as a precursor for bile acids. The bile acids, natural detergents, are secreted by the liver and enter the intestinal tract where they aid in the digestion and absorption of fats. The bile acids are then re-absorbed from the intestine and returned to the liver. The bile acids are secreted into the intestine again and the process repeats. Although the system operates very efficiently, a small percentage of bile acids escape recycle and are eliminated through the feces. The amount of bile acids lost is replenished by conversion of cholesterol to bile acids. The bile acid sequestrant resins interrupt the bile acid cycle by binding to the bile acids and thereby increasing the amount of bile acids excreted in the feces.
Bile acid sequestrant resins have been administered orally to reduce blood cholesterol levels. Well known resins include cholestyramine, a synthetic, strongly basic anion exchange resin containing quaternary ammonium functional groups which are attached to a styrene-divinylbenzene copolymer, and colestipol, N-(2-aminoethyl)-1,2-ethanediamine polymer with (chloromethyl)oxirane. The mechanism for lowering cholesterol by consumption of these sequestrants is well known.
Although the efficacy of bile acid sequestrant resins, and particularly cholestyramine, is well known, administration of the resin is unpleasant because the resin is not palatable and must be taken in relatively high doses of 4 to 24 grams per day. For most therapeutic treatment, the resin is generally suspended in a beverage such as water or in fruit juices and the beverage is consumed to supply cholestyramine to the intestinal system. Examples of such beverage resin suspensions are disclosed in U.S. Pat. Nos. 3,974,272; 4,172,120 and 4,064,234.
In addition to its unpalatable taste which is exacerbated by the requirement of high dosages of consumption of resin to enable efficacy, high levels of cholestyramine and other bile acid sequestrant resins can cause several side effects, such as constipation.
Thus, there exists a need in the art to treat hypercholesterolemia by utilizing a bile acid sequestrant resin containing composition wherein the composition exhibits a higher degree of in vivo efficacy.
Hoffman et al., "Sampling Intestinal Content with a Sequestering Capsule," Mayo Clin Proc, Mar 1976, Vol. 51 describes a non-invasive technique for sampling bile acid in man where a cholestyramine resin suspension is filled into a 1 cm dialysis tubing which is sealed with a surgical clip and placed in an opaque 00 gelatin capsule. The capsule is administered to humans as a means for studying bile acid metabolism. There is no suggestion in the paper of using the capsule to administer a bile acid sequesterant resin or using a dialysis tubing which selectively admits low molecular weight materials from the intestine.